The long-term objective of this research is the development of dual-mode ultrasound array (DMUA) systems for the noninvasive treatment of cancer tumors using high intensity focused ultrasound (HIFU). These DMUA systems will be capable of generating therapeutic pulsed HIFU beams for localized destruction of targeted tissue and intermittently imaging the targeted region and it's surroundings in real- time using the same array elements. Using a piezocomposite 1-MHz 64-element DMUA prototype, we have demonstrated the feasibility of using the same transducer for imaging and therapy. Using appropriate field simulation tools, we propose to develop design procedures that will allow the simultaneous optimization of DMUAs for both imaging and therapy. Furthermore, we propose to design and build the real-time beamforming and signal processing capabilities to allow the use of DMUA systems in realistic real-time testing. This will be a necessary step before planning to perform in vivo animal testing. We will focus our efforts on the development of image-based feedback that will help refocus the HIFU beam in the presence of tissue heterogeneity and strongly scattering objects. This will allow the use of DMUA systems for the noninvasive treatment of tumors in abdominal organs such as liver and kidney (by refocusing in the presence of the ribs). In addition, we will develop parametric imaging methods to assess the treated tissue before, during, and after the application of therapeutic HIFU dose. In particular, we will investigate the feasibility of imaging local absorption, perfusion, and viscoelastic properties (shear modulus and shear viscosity) during sub-therapeutic exposure to HIFU beams at the target. These parametric imaging methods will be developed for both DMUA-based imaging and commercial ultrasound scanners for image guidance. This is necessary to provide better understanding of the limitations imposed by the (possibly) limited bandwidth and beamforming capabilities of DMUAs. In addition, quantitative ultrasonic imaging is still needed if ultrasound is to remain viable as an image-guidance modality. We envision a fully operational real-time DMUA system with image-based feedback will be developed and fully tested in vitro during the funding period of the proposed research. Once this system is in place, we plan to establish collaborations with clinical colleagues to test this system in vivo in preparation for targeted clinical applications. If we are successful, our DMUA system will add, at a minimum, significant value to other image-guidance modalities, e.g. MRI, CT, or diagnostic ultrasound. However, if the quality of DMUA- based images can be brought to levels where quantitative spatially accurate imaging can be assured, then DMUA systems will provide a unique approach to image-guided surgery. Specifically, we will have self- guided therapeutic arrays capable of assessing the target region before, during, and after lesion formation. The image-based feedback will help maximize the therapeutic dose at the target while minimizing collateral damage to intervening critical tissue structures that may interact with the therapeutic HIFU beam. This will be essential for the noninvasive application of therapeutic HIFU to liver and kidney tumors. PUBLIC HEALTH RELEVANCE: A new generation of ultrasound array systems for the noninvasive treatment of cancer and other tissue abnormalities will be developed. The distinguishing characteristic of the system is its capability to deliver high intensity focused ultrasound (HIFU) to the target tissue and provide image feedback from the treatment volume using the same array elements. The inherent registration between the therapeutic and imaging coordinate systems will lead to a new paradigm in image-guided surgery. Spatially accurate image- based feedback will improve the treatment efficacy by refocusing the HIFU beam in the presence of tissue heterogeneities and other strongly scattering obstacles. Furthermore, parametric imaging of the tissue response at the exact location of the therapeutic HIFU beam before, during, and after the application of HIFU provides a unique opportunity to monitor the progression of the treatment and potentially assess its outcome.